Background: This paper aims to investigate the metabolic impact of walnut meal extracts rich in polyphenols (WMP) on high fat diet (HFD)-fed rats and to determine whether the lipid-lowering effects are related to modulations of the gut microbiota. SD rats were fed a standard chow diet or an HFD for 18 weeks. After 6 weeks, the HFD rats were supplemented with 750mg WMP/kg body weight and the vehicle for 12 weeks. The structure of gut microbiota was assessed by analyzing 16S rDNA sequences.Results: WMP suppressed the weight gain and visceral obesity. WMP treatment also improved lipid profiles and increased antioxidative activities. WMP fully reversed hepatic steatosis with upregulation of adipocytokines involved in lipid catabolism (e.g. adiponectin, PPAR-γ, visfatin, CEBPα), and increased the activity of lipoprotein lipase, hormone-sensitive lipase, in which were associated with glucose tolerance improved and insulin resistance mitigated. As revealed by 16S rDNA sequencing, WMP restored the diversity of intestinal flora reduced by HFD, dramatically reduced the abundance of Fusobacterium varium and Enterobacteriaceae, reversed and sharply raised the abundance of Lachnospiraceae UCG005 and Akkermansia decreased by HFD.Conclusion: Our findings demonstrated that WMP suppressed the weight gain and adiposity in HFD-fed rats, and fully reversed HFD diet-induced insulin resistance and hepatic steatosis while dramatically reduced the abundance of Fusobacteriaceae and Enterobacteriaceae, underscoring the gut-liver axis as a primary target of walnut polyphenols.